ProjectSummary Thebroadgoalofthisworkistounderstandhowembryoscoordinatethefusionand separationofepithelialsheetsduringearlydevelopment.Aprimaryexampleofthisoccurs duringneuraltubeclosurewhenthelateraledgesoftheneuralprimordium(theneural folds)meetatthemidlineandfusetoseparateaclosedneuraltubefromacontinuous overlyingepidermis.Thisprocessisknownaszipperingbecauseitproceedsdirectionally frominitialpointsalongtheanterior-?posterioraxisfrominitialpointsofcontact.Zippering iscommontomanyformsofepithelialfusion,buthowitworksispoorlyunderstood.Akey challengeistounderstandhowtheforcesareproducedthatpulltheneuralfoldstogether anddrivethezipperforwardandhowtheseforcesarecontrolledinspaceandtimeto achievea WewilladdressthesechallengesusingtheinvertebratechordateCionaintestinalisasa modelsystem.Cionaoffersauniquelytractableopportunitytostudyaverysimpleformof epithelialzipperingandneuraltubeclosureinvolvingveryfewcellswithwell-?developed toolsformoleculargeneticmanipulation,transgenesisandhigh-?speedliveimaging.In recentwork,weshowedthatzipperingispoweredbyadynamicsequenceofactomyosin-? dependentjunctioncontractionsthatsweepsfromposteriortoanterioralongthelateral edgesoftheneuralplate.Wewilluseahighlyinterdisciplinarycombinationofquantitative imaging,experimentalmanipulationsandpredictivemodelingtoaskthefollowing questions: (1) Howisthiswaveofcontractioncontrolledthroughcell-?cellsignalingalongthe Neural/Epidermalboundaryandbetweenneuralfoldsacrossthemidline? (2) Whatarethesignalingpathwaysthatmediatethiscontrol? (3) Howarelocalsignaling,forceproductionandtissueremodelingintegratedto createaself-?propagatingwaveofjunctioncontractionandtissuefusionacross theembryo? Becausemanyofthemoleculesthatmediatecell-?cellsignalingandforceproductionare highlyconservedacrossthemetazoa,ourworkwillhavedirectrelevancetounderstanding neuraltubeclosureandtissuefusiongenerallyinhigherchordates,anditwillprovidenew insightsintohowfailuresinthisprocesscanleadtobirthdefectsinhumans.